Abstract

P. gingivalis is a Gram-negative anaerobe that is considered one of the etiologic agents of certain types of periodontal disease. In addition, there is significant evidence that P. gingivalis may play a role in the progression of cardiovascular diseases (CVD), especially atherosclerosis. We have previously reported that P. gingivalis can invade primary human cardiovascular endothelial cells (HCAEC), the cells where the initial events of atherosclerosis take place. We have determined that once inside the cells, P. gingivalis usurps the autophagic pathway of the HCAEC and uses autophagic vesicles as its privileged niche where it survives and replicates. The purpose of the current application is to more completely define the communication and interactions at the molecular level between the bacteria and its host. Based on our previous studies, our hypothesis is that P. gingivalis secretes or expresses proteins that are required for adhesion/internalization, trafficking and persistence in HCAEC.
In Aim 1, we will identify those proteins that are essential for P. gingivalis adhesion/internalization, trafficking and persistence in HCAEC by mutant analysis.
In Aim 2, we will more fully characterize the proteins verified to be adhesins or essential for internalization and determine if internalization proceeds via lipid rafts.
In Aim 3, we will study bacterial trafficking within HCAEC by identifying and characterizing those proteins essential for activating autophagy and trafficking the bacterium away from the lysosomes and to the replicating vacuoles.
In Aim 4, we will examine bacterial persistence by identifying and characterizing those proteins that promote survival of HCAEC. Finally, in Specific Aim 5, we will characterize the expression profiles in HCAEC infected with wild type and mutant strains of P. gingivalis. This comprehensive study will provide us essential information on the molecular events required for invasion of endothelial cells by this intracellular pathogen. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE013545-06A1
Application #
7033689
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2000-04-15
Project End
2011-02-28
Budget Start
2006-03-02
Budget End
2007-02-28
Support Year
6
Fiscal Year
2006
Total Cost
$479,968
Indirect Cost

  Institution

Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Xie, Gary; Chastain-Gross, Ryan P; Bélanger, Myriam et al. (2017) Genome Sequence of Porphyromonas gingivalis Strain A7A1-28. Genome Announc 5:
Chastain-Gross, Ryan P; Xie, Gary; Bélanger, Myriam et al. (2017) Genome Sequence of Porphyromonas gingivalis Strain 381. Genome Announc 5:
Chastain-Gross, Ryan P; Xie, Gary; Bélanger, Myriam et al. (2015) Genome Sequence of Porphyromonas gingivalis Strain A7436. Genome Announc 3:
Xie, Gary; Chastain-Gross, Ryan P; Bélanger, Myriam et al. (2015) Genome Sequence of Porphyromonas gingivalis Strain AJW4. Genome Announc 3:
Reyes, Leticia; Eiler-McManis, Eileen; Rodrigues, Paulo H et al. (2013) Deletion of lipoprotein PG0717 in Porphyromonas gingivalis W83 reduces gingipain activity and alters trafficking in and response by host cells. PLoS One 8:e74230
Bélanger, Myriam; Kozarov, Emil; Song, Hong et al. (2012) Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells. Anaerobe 18:128-34
Rodrigues, Paulo H; Reyes, Leticia; Chadda, Amandeep S et al. (2012) Porphyromonas gingivalis strain specific interactions with human coronary artery endothelial cells: a comparative study. PLoS One 7:e52606
Van Hemert, Jonathan R; Recker, Erica N; Dietrich, Deborah et al. (2012) Human ?-defensin-3 alters, but does not inhibit, the binding of Porphyromonas gingivalis haemagglutinin B to the surface of human dendritic cells. Int J Antimicrob Agents 40:75-9
Walters, S; Rodrigues, P; Bélanger, M et al. (2009) Analysis of a band 7/MEC-2 family gene of Porphyromonas gingivalis. J Dent Res 88:34-8
Abranches, J; Zeng, L; Bélanger, M et al. (2009) Invasion of human coronary artery endothelial cells by Streptococcus mutans OMZ175. Oral Microbiol Immunol 24:141-5

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